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Biomedical subjects

Lanny G Close

Publications and source records attributed to Lanny G Close.

5 recordsLinked to original sources

PIK3CA mutations in head and neck squamous cell carcinoma.

PURPOSE: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic alpha (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC. EXPERIMENTAL DESIGN: More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens. RESULTS: We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A --> G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples. CONCLUSIONS: These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.

Adult↗

Combined modality treatment of Ewing's sarcoma of the maxilla.

BACKGROUND: Primary bone sarcomas arising in osseous structures of the head and neck are rare. These tumors are often incompletely resected and treated with radiotherapy for local control. METHODS: We report a case of a 9-year-old girl with a maxillary Ewing's sarcoma. This patient was successfully treated with neoadjuvant chemotherapy followed by surgical resection and prosthetic reconstruction of the primary site. The surgical approach that was used consisted of a subtotal maxillectomy by means of a facial degloving approach, sparing the orbital contents and the inferior orbital rim and orbital floor. RESULTS: This approach produced excellent cosmetic, functional, and oncologic outcome. The patient remains without evidence of disease recurrence more than 4 years after surgery. CONCLUSIONS: This case illustrates a novel surgical approach to the resection of a maxillary Ewing's sarcoma and highlights the need for a multidisciplinary team approach to the management of head and neck sarcomas in children.

Antineoplastic Combined Chemotherapy Protocols↗

"Balanced" orbital decompression for severe Graves' orbitopathy: technique with treatment algorithm.

BACKGROUND: Graves' orbitopathy can produce proptosis, compressive optic neuropathy, and extraocular motility abnormalities; symptoms result from an increase in orbital volume due to expansion of intraorbital fat, with or without extraocular muscle involvement. STUDY DESIGN: We conducted a chart review of patients who underwent orbital decompression to treat Graves' orbitopathy. Twenty-two orbits (13 patients) underwent orbital bone decompression, of which 17 orbits (9 patients) underwent the combined medial and lateral "balanced" decompression. RESULTS: All patients had significant improvement with an average decrease in proptosis of 5.9 mm in the balanced decompression group. Restoration of normal optic nerve function was achieved in all patients with compressive optic neuropathy. Diplopia was noted in 4 patients (30.7%) preoperatively. Two patients had new postoperative diplopia (15.35%). CONCLUSION: In our experience, "balanced" decompression results in a reduction of proptosis and improved optic nerve function and has a low incidence of complications.

Adult↗

Laryngeal adductor reflex and pharyngeal squeeze as predictors of laryngeal penetration and aspiration.

OBJECTIVES: The contribution of laryngopharyngeal (LP) sensory deficits to the outcome of swallowing and the relationship between sensory and motor deficits in the laryngopharynx is unclear. The study purpose is to determine if patients with LP sensory and motor deficits are at increased risk for laryngeal penetration and aspiration during swallowing, and to determine the relationship between pharyngeal motor weakness and LP sensory deficits. MATERIALS AND METHODS: Endoscopic evaluation of swallowing with sensory testing was performed on 122 dysphagic patients who were prospectively divided into two groups. The control group was 76 patients with normal sensitivity, determined by an intact laryngeal adductor reflex (LAR) on air pulse stimulation of the mucosa innervated by the superior laryngeal nerve. The study group was 46 patients with severe sensory deficits, determined by an absent LAR. Each group was given puree followed by thin liquid, noting presence or absence of laryngeal penetration and aspiration. Pharyngeal muscle strength was assessed by noting presence or absence of pharyngeal contraction during voluntary adduction of the vocal folds (pharyngeal squeeze). RESULTS: In control subjects, with purees, 6 of 76 (7.90%) penetrated and 3 of 76 (3.94%) aspirated; with thins, 26 of 76 (34.2%) penetrated and 13 of 76 (17.1%) aspirated. In the absent LAR group, with purees, 39 of 46 (84.8%) penetrated and 32 and 46 (69.6%) aspirated; with thins, 46 of 46 (100%) penetrated and 43 of 46 (93.5%) aspirated. For both consistencies, the differences in prevalence of penetration and aspiration between groups was significant (P <.0001, chi2). In control subjects, pharyngeal squeeze was impaired in 17 of 76 (22.4%), with penetration of puree in 6 of 17 (35.3%) and aspiration in 3 of 17 (17.6%). In the absent LAR group, squeeze was impaired in 41 of 46 (89.1%), with penetration of puree in 39 of 41 (95.1%) and aspiration in 32 of 41 (78.0%). The difference in the prevalence of pharyngeal weakness between groups was significant (P <.0001). The difference in the prevalence of penetration and aspiration was higher in the absent LAR/impaired contraction cohort than in the normal sensation/impaired contraction cohort (P <.0001). CONCLUSION: Absence of the LAR and impaired pharyngeal squeeze puts patients with dysphagia at high risk for laryngeal penetration and aspiration compared with patients with an intact LAR and intact pharyngeal squeeze. There is a strong association between motor and sensory deficits in the laryngopharynx.

Adult↗